There has long been a need for a representative animal model to test the efficacy of proposed new anti-neoplastic agents without having to perform long term xenograft studies. The present in vivo models with which potential anti-neoplastic agents are tested involve inplanting tumor cells into a non-human animal, treating the animal with the proposed new anti-neoplastic agent, and then monitoring the animals to determine the effect of treatment on the growth of the tumor. To aid the visualization of the tumor cells against the background of the host cells, many in vivo models use tumor cells stably transfected with a reporter gene such as the luciferase family and aequorin family of bioluminescent molecules.
A major drawback of these in vivo models, in the development of antitumor agents, is the limited troughput, i.e. a large number of animals and a large amount of proposed antitumor compound are required. Furthermore, these in vivo models are time consuming, as they require sufficient time for the implanted tumor to grow in the animal. Accordingly, an improved model was recently proposed by Lassota P. in the International Patent Application (PCT/EP02/00106) published as WO 02/055742 on 18 Jul. 2002. In this model the tumor cells with a reporter gene, which is activated by the antitumoral agent, are grown in a biocompatible semi-permeable encapsulation device, which is implanted in the non-human animal and removed after exposure of the animal to the compound to be tested. However, in view of the artificial environment of the tumor cells it is questionable whether the response of the tumor cells truly mimics the in vivo situation where a compound needs to get into circulation, infiltrate the tumor tissue and exert its biological effect.
Hence, to fulfil the need for an animal model for human neoplastic disease, which is without the above-mentioned deficiencies, the present invention discloses a new animal model that has the ability to truly mimic the pharmacological activity of a proposed anti-neoplastic compound in vivo. A model that allows monitoring the anti-neoplastic activity of a compound in a non-invasive way and that comprises the use of stably transformed tumor cells, which had been transfected with an expression vector containing a reporter gene operably linked to a promoter that also controls expression of a protein that is associated with tumor regression. In order to provide the desired animal model, the cells should;                retain the capability to form a tumor when implanted or injected into the animal;        generate a signal that parallels the endogenous response of a protein associated with tumor regression;        generate a signal with a good signal to noise ratio, to allow a real time analysis of the kinetic effect of drug substances in vivo;        generate a signal with a good reproducibility to provide a low variability between animals; and        generate a signal that allows non-invasive imaging of the induced response.        